1. Field of the Invention
This invention relates to novel phosphonate-nucleotide ester derivatives or pharmaceutically acceptable salts thereof. More particularly, it relates to novel phosphonate-nucleotide ester derivatives or pharmaceutically acceptable salts thereof which can be orally administered as antiviral agents.
2. Background of the Invention
Infectious viral diseases have been recognized as medically important problems. For treatment of such diseases, drugs having antiviral activity but no inhibitory activity on growth of normal cell lines have been developed. For example, 9-(2-phosphonylmethoxy)ethyladenine (PMEA), 9-(2-phosphonylmethoxy)ethyl-2,6-diaminopurine (PMDAP) etc. have been reported to be effective on herpes simplex viruses type-I and II (HSV-1 and HSV-2), human immunodeficiency virus (HIV), hepatitis B virus (Yokota et al., Antimicrob. Agents Chemother., 35, 394 (1991); Votruba et al., Mol. Pharmacol., 32, 524 (1987)].
The problems of these nucleotides and ionic organophosphate esters are their deficiency of oral absorptivity [see, De Clercq et al., Antimicrob. Agents Chemother., 33, 185 (1989)]. Therefore, these compounds should be parenterally administered, for example, by intravenous or intramuscular injection, to attain sufficient blood concentration to elicit their effect.
However, it is difficult to apply treatment utilizing parenteral administration unless the subject is in a hospital. Accordingly, it is not a preferred method to treat subjects suffering from altricious diseases such as AIDS and HBV diseases. Accordingly, there required development of drugs which have antiviral activity and can be parenterally administered. Up to date, no drugs have been put into practical use.